The 2022 Tandem Meetings | Using dual-targeting CAR-Ts to overcome CAF-induced CAR-T resistance in multiple myeloma
Reona Sakemura, MD, PhD, Mayo Clinic, Rochester, MN, explains how we can overcome cancer-associated fibroblast (CAF)-induced CAR-T resistance using dual-targeting CAR-Ts in multiple myeloma. Whilst CAR-T therapy has shown remarkable efficacy, the durability of response is still limited. This has been attributed to the immunosuppressive tumor microenvironment, which is composed of several cells including CAFs. Pre-clinical experiments have shown that BCMA-directed CAR-Ts exhibit impaired function in multiple myeloma tumor microenvironment mouse models. Further experiments with dual-targeting CAR-Ts against BCMA and SLAMF7 showed improved anti-tumor efficacy and prolonged CAR-T persistence. These dual targeting CAR-Ts will be evaluated in a Phase I/II clinical trial in patients with relapsed/refractory (R/R) multiple myeloma. This interview took place at the Transplantation & Cellular Therapy (TCT) Meetings of ASTCT™ and CIBMTR® 2022 in Salt Lake City, Utah.
